Clinical significance of class II HLA genes (DRB1, DQA1 and DQB1) in tick-born encephalitis

Tick-borne encephalitis is a natural endemic disease which is widely spread in Russia. The purpose of the study was to determine clinical significance of HLA class II genes in tick-borne encephalitis. We observed 75 patients with tick-borne encephalitis admitted to the Kirov Hospital of Infectious Diseases and district hospitals over 2020-2023. Molecular typing of the HLA genes DRB1, DQA1 and DQB1 was carried out using PCR technique, with a set of commercial sequence-specific primers (“DNA-Technology”, Russian Federation). The febrile form of tick-borne encephalitis was noted in 41.3% of patients; focal, in 34.7%; meningeal, in 16.0%, inapparent, in 8% of cases. The comparison group for HLA DRB1 locus included 1528 practically healthy individuals from the same population. Comparison group for HLA DQA1 and DQB1 genes comprised 133 persons. The study has revealed a number of HLA class II genes, which are found significantly more often in TBE patients, rather than in control group (DRB1*1 (χ² = 12.2; p_c < 0.01), DRB1*4 (χ² = 6 .4; p_c < 0.05), DRB1*7 (χ² = 11.7; p_c < 0.01), DRB1*8 (χ² = 4.6; p_c < 0.05), DRB1*13 (χ² = 7.7; p_c < 0.01), DRB1*15 (χ² = 9.3; p_c < 0.01), DRB1*16 (χ² = 14.3; p_c < 0.01), DQA1*0102 (χ² = 7.6; p_c < 0.01), DQB1*0401-2 (χ² = 3.9; p_c < 0.05), DQB1*0502-4 (χ² = 8.1; p_c < 0.01). Among HLA class II haplotypes, the susceptibility to the development of tick-borne encephalitis was determined by the combinations DRB1*08-DQA1*0401-DQB1*401/402 (χ² = 5.7; p_c < 0.05), DRB1*09-DQA1*0301- DQB1*303 (χ² = 5.7; p_c < 0.05) and DRB1*16-DQA1*0102-DQB1*502 (χ² = 7.4; p_c < 0.01). Carriage of the DRB1*15 gene was most risky for development of febrile form of tick-borne encephalitis, (χ² = 7.8; p_c < 0.01; RR = 3.1). Occurrence of three-locus haplotypes DRB1*09-DQA1*0301-DQB1*303 (χ² = 8.8; p_c < 0.01), and DRB1*16-DQA1*0102-DQB1*502 (χ² = 5.0; p_c < 0.05) was associated with increased risk of developing a febrile form of TE by 14.5 and 10.9 times, respectively. In patients with meningeal form of EC, compared with healthy individuals, the gene variants DRB1*08 (χ² = 12.9; p_c < 0.01), DQA1*401 (χ² = 3.9; p_c < 0.05), DQB1*401/402 (χ² = 9.1; p_c < 0.01) were significantly more common. The presence of a threelocus haplotype DRB1*16-DQA1*0102-DQB1*502 (χ² = 10.9; p_c < 0.01) increases the risk of developing a focal TBE by 17.7 times. Thus, tick-borne encephalitis is associated with certain HLA class II alleles, which may be used as a prognostic criterion for development of different clinical forms of tick-borne encephalitis, or tick-borne encephalitis in general.

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